Maternal Plasma Metabolic Profile Demarcates a Role for Neuroinflammation in Non-Typical Development of Children

Schmidt, Rebecca J.; Liang, Donghai; Busgang, Stefanie A.; Curtin, Paul; Giulivi, Cecilia R

doi:10.3390/metabo11080545

Cited by 10 publications

(8 citation statements)

References 142 publications

(159 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The existing targeted metabolomics studies have focused on individual metabolites in the pathways related to polyunsaturated fatty acids (PUFA) and inflammation, and have focused on autism spectrum disorders (ASD) or traits and neurodevelopmental delay [18][19][20]. Similarly, while the untargeted metabolomic studies have covered a much larger number of metabolic pathways, they are also limited to studying individual metabolites and ASD or non-typical neurodevelopment [21,22].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, none of the existing studies have taken advantage of multivariate supervised analytical methods that have become the mainstream of metabolomics analyses, such as orthogonal partial least squares (O-PLS) analysis. Hence, variation in the individual metabolites of the mother during pregnancy examined in the previous studies [ 18 – 22 ] may not have necessarily reflected the metabolomic variation specific to maternal obesity or higher BMI during pregnancy, and has not accounted for the correlated nature of the metabolomic measures. O-PLS overcomes these limitations as it reduces data dimensions and finds latent variables that maximize the correlation between the predictors and the outcome, while taking advantage of an orthogonal signal correction filter to remove variation in the predictors that are not explained by the outcome [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in children

et al. 2022

View full text Add to dashboard Cite

Maternal pre-pregnancy obesity and/or higher body mass index (BMI) have been associated with neurodevelopmental and mental health adversities in children. While maternal metabolomic perturbations during pregnancy may underpin these associations, the existing evidence is limited to studying individual metabolites, not capturing metabolic variation specific to maternal BMI, and not accounting for the correlated nature of the metabolomic measures. By using multivariate supervised analytical methods, we first identified maternal early-pregnancy BMI-associated metabolomic component during pregnancy. We then examined whether this component was associated with mental and behavioral disorders in children, improved the prediction of the child outcomes over maternal BMI, and what proportion of the effect of maternal BMI on the child outcomes this component mediated. Early-pregnancy BMI of 425 mothers participating in the PREDO study was extracted from the national Medical Birth Register. During pregnancy, mothers donated up to three blood samples, from which a targeted panel of 68 metabolites were measured. Mental and behavioral disorders in children followed-up from birth until 8.4–12.8 years came from the Care Register for Health Care. Of the 68 metabolites averaged across the three sampling points, 43 associated significantly with maternal early-pregnancy BMI yielding a maternal early-pregnancy BMI-associated metabolomic component (total variance explained, 55.4%; predictive ability, 52.0%). This metabolomic component was significantly associated with higher hazard of any mental and behavioral disorder [HR 1.45, 95%CI(1.15, 1.84)] and relative risk of having a higher number of co-morbid disorders [RR 1.43, 95%CI(1.12, 1.69)] in children. It improved the goodness-of-model-fit over maternal BMI by 37.7–65.6%, and hence the predictive significance of the model, and mediated 60.8–75.8% of the effect of maternal BMI on the child outcomes. Maternal BMI-related metabolomic perturbations during pregnancy are associated with a higher risk of mental and behavioral disorders in children. These findings may allow identifying metabolomic targets for personalized interventions.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in children

et al. 2022

View full text Add to dashboard Cite

show abstract

“… 37 Lower maternal 3-OHB concentrations in the third trimester might indicate dysregulated maternal lipid metabolism, resulting in reduced availability of important lipid substrates for brain development. While this analysis was limited to the polar metabolome, a 2021 study 38 reporting on the untargeted metabolomic analysis of maternal third trimester plasma showed that higher levels of fatty acids involved in lipid biosynthesis were associated with reduced risk of non-TD in the MARBLES cohort. Taken together, these findings suggest that disturbed lipid metabolism during late pregnancy could play a role in the etiology of non-TD.…”

Section: Discussionmentioning

confidence: 99%

Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit

Parenti,

Schmidt,

Tancredi

et al. 2024

JAMA Netw Open

Self Cite

View full text Add to dashboard Cite

ImportanceDisturbances in maternal, placental, and fetal metabolism are associated with developmental outcomes. Associations of maternal, placental, and fetal metabolism with subsequent neurodevelopmental outcomes in the child are understudied.ObjectiveTo investigate the metabolic associations within the maternal-placental-fetal unit and subsequent neurodevelopmental outcomes in younger siblings of children with autism spectrum disorder (ASD).Design, Setting, and ParticipantsThis cohort study was conducted within a subset of the Markers of Autism Risk in Babies, Learning Early Signs (MARBLES) cohort. MARBLES is a prospective birth cohort of younger siblings of children with ASD assessed for neurodevelopmental outcomes at approximately age 36 months. Participants in MARBLES were recruited through the UC Davis MIND Institute. This subset of the MARBLES cohort included younger siblings born between 2009 and 2015. Maternal third trimester serum, placental tissue, and umbilical cord serum samples were collected from participants. Only pregnancies with at least 2 of these sample types were included in this analysis. Data analysis was conducted from March 1, 2023, to March 15, 2024.ExposuresQuantitative metabolomics analysis was conducted on maternal third trimester serum, as well as placental tissue and umbilical cord serum collected at delivery.Main Outcomes and MeasuresUsing the Autism Diagnostic Observation Schedule and Mullen Scales of Early Learning, outcomes were classified as ASD, other nontypical development (non-TD), and typical development (TD).ResultsThis analysis included 100 maternal serum samples, 141 placental samples, and 124 umbilical cord serum samples from 152 pregnancies (median [IQR] maternal age, 34.6 [30.8-38.3] years; median [IQR] gestational age, 39.0 [38.6-39.7] weeks; 87 [57.2%] male infants). There was no evidence that the maternal third trimester serum metabolome was significantly associated with the other metabolomes. The placental and cord serum metabolomes were highly correlated (first latent variate pair: R2 = 0.75; P &lt; .001) and the variate scores for each tissue were significantly associated with reduced risk of non-TD (placenta: relative risk [RR], 0.13; 95% CI, 0.02-0.71; cord: RR, 0.13; 95% CI, 0.03-0.70) but not ASD (placenta: RR, 1.09; 95% CI, 0.42-2.81; cord: RR, 0.63; 95% CI, 0.23-1.73) compared with the TD reference group.Conclusions and RelevanceIn this cohort study of children with high familial risk of ASD, placental and cord serum metabolism at delivery were highly correlated. Furthermore, placental and cord serum metabolic profiles were associated with risk of non-TD.

show abstract

“…Additionally, the cohort includes children who did not develop ASD, but who were otherwise non-typically developing. A recent study of maternal third trimester plasma collected as part of the MARBLES study has identified alterations in the prostaglandin pathway related to non-typical development [44].…”

Section: Introductionmentioning

confidence: 99%

Maternal Serum and Placental Metabolomes in Association with Prenatal Phthalate Exposure and Neurodevelopmental Outcomes in the MARBLES Cohort

et al. 2022

Self Cite

View full text Add to dashboard Cite

Prenatal exposure to phthalates, a family of endocrine-disrupting plasticizers, is associated with disruption of maternal metabolism and impaired neurodevelopment. We investigated associations between prenatal phthalate exposure and alterations of both the maternal third trimester serum metabolome and the placental metabolome at birth, and associations of these with child neurodevelopmental outcomes using data and samples from the Markers of Autism Risk in Babies Learning Early Signs (MARBLES) cohort. The third trimester serum (n = 106) and placental (n = 132) metabolomes were investigated using 1H nuclear magnetic resonance spectroscopy. Children were assessed clinically for autism spectrum disorder (ASD) and cognitive development. Although none of the urinary phthalate metabolite concentrations were associated with maternal serum metabolites after adjustment for covariates, mixture analysis using quantile g-computation revealed alterations in placental metabolites with increasing concentrations of phthalate metabolites that included reduced concentrations of 2-hydoxybutyrate, carnitine, O-acetylcarnitine, glucitol, and N-acetylneuraminate. Child neurodevelopmental outcome was not associated with the third trimester serum metabolome, but it was correlated with the placental metabolome in male children only. Maternal phthalate exposure during pregnancy is associated with differences in the placental metabolome at delivery, and the placental metabolome is associated with neurodevelopmental outcomes in males in a cohort with high familial ASD risk.

show abstract

Maternal Plasma Metabolic Profile Demarcates a Role for Neuroinflammation in Non-Typical Development of Children

Cited by 10 publications

References 142 publications

Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in children

Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in children

Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit

Maternal Serum and Placental Metabolomes in Association with Prenatal Phthalate Exposure and Neurodevelopmental Outcomes in the MARBLES Cohort

Contact Info

Product

Resources

About